KCNQ3 activation by the naturally occurring phenol, eugenol.

IF 1.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Adrián Rivera-Ruedas, Alejandro R Medina-Vilchis, Juan J Romero-Tovar, Gema R Cristóbal-Mondragón, Victor De la Rosa
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引用次数: 0

Abstract

Pharmacological targeting of ion channels represents a crucial avenue for pain management. The KCNQ family of ion channels plays a significant role in controlling neuronal excitability and the generation and propagation of pain-related nerve impulses, mitigating excessive electrical signaling and limiting the transmission of pain signals. Eugenol has a variety of biological activities, including analgesic and anti-inflammatory properties. When used in conjunction with the anti-inflammatory drug diclofenac, eugenol demonstrates enhanced analgesic efficacy in animal models. We investigated the effects of eugenol on KCNQ ion channels. Eugenol acts as a KCNQ2/3 activator, shifting the voltage dependency to negative potentials, most of the activation can be explained by the effect on the KCNQ3, molecular docking simulation and mutagenesis experiments suggest that the binding pocket of eugenol is located at the top of the voltage-sensing domain. We also show that eugenol is a weak activator of the TRPV1 channel yet inhibits the capsaicin and acidic pH-activated current. Diclofenac also inhibits the TRPV1 channel current. In cells co-expressing KCNQ2/3 and TRPV1, eugenol and diclofenac limit the extent of membrane depolarization. Altogether, we report a new target for eugenol that adds to its wide array of biological activities, including its role in modulating acute pain.

KCNQ3被天然存在的苯酚、丁香酚激活。
离子通道的药理靶向是疼痛管理的重要途径。KCNQ离子通道家族在控制神经元兴奋性和疼痛相关神经冲动的产生和传播、减轻过度电信号和限制疼痛信号的传递等方面发挥着重要作用。丁香酚具有多种生物活性,包括镇痛和抗炎特性。当与抗炎药双氯芬酸联合使用时,丁香酚在动物模型中显示出增强的镇痛效果。研究了丁香酚对KCNQ离子通道的影响。丁香酚作为KCNQ2/3激活剂,将电压依赖性转移到负电位,大部分激活可以通过对KCNQ3的影响来解释,分子对接模拟和诱变实验表明丁香酚的结合口袋位于电压感应域的顶部。我们还发现丁香酚是TRPV1通道的弱激活剂,但可以抑制辣椒素和酸性pH激活电流。双氯芬酸也抑制TRPV1通道电流。在共表达KCNQ2/3和TRPV1的细胞中,丁香酚和双氯芬酸限制了膜去极化的程度。总之,我们报告了丁香酚的新靶点,增加了其广泛的生物活性,包括其在调节急性疼痛中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
4.80%
发文量
90
审稿时长
3-8 weeks
期刊介绍: Published since 1929, the Canadian Journal of Physiology and Pharmacology is a monthly journal that reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership. The journal periodically publishes a “Made In Canada” special section that features invited review articles from internationally recognized scientists who have received some of their training in Canada.
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